Golvatinib (E7050)

製品コードS2859 バッチS285901

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C33H37F2N7O4
分子量 633.69 CAS No. 928037-13-2
Solubility (25°C)* 体外 DMSO 20 mg/mL (31.56 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
30%propylene glycol 5%Tween80 65%D5W
30.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Golvatinib (E7050) is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, does not inhibit bFGF-stimulated HUVEC growth (up to 1000 nM). Phase 1/2.
in vitro In vitro studies indicate that E7050 potently inhibits phosphorylation of both c-Met and VEGFR-2. E7050 also potently represses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF. [1] E7050 circumvents resistance to all of the reversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Akt pathway in vitro. E7050 also prevents the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF. [2]
in vivo In vivo studies using E7050 shows inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors, and strong inhibition of tumor growth and tumor angiogenesis in xenograft models. Treatment of some tumor lines containing c-met amplifications with high doses of E7050 (50–200 mg/kg) induces tumor regression and disappearance. In a peritoneal dissemination model, E7050 shows an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice. [1] In another xenograft model research, tumors produced by HGF-transfected Ma-1 (Ma-1/HGF) cells are more angiogenic than vector control tumors and shows resistance to ZD1839. E7050 alone inhibits angiogenesis and retards growth of Ma-1/HGF tumors. E7050 combined with ZD1839 induces marked regression of tumor growth. [3]

プロトコル(参考用のみ)

キナーゼアッセイ Western blot analysis
The phosphorylation status of c-Met and VEGFR-2 is detected by Western blot analysis. For c-Met, MKN45 cells are incubated with a serial dilution of E7050 in complete medium at 37 °C for 2 h. For VEGFR-2, HUVEC are starved with human endothelial serum free medium containing 0.5% FBS for 24 h. Subsequently HUVEC are incubated with a serial dilution of E7050 for 1 h and then incubated with 20 ng/mL of human VEGF for 5 min. Cells are lysed by lysis buffer (50 mM HEPES [pH 7.4], 150 mM NaCl, 10% glycerol, 1% Triton X-100, 1.5 mM MgCl2, 1 mM EDTA [pH 8.0], 100 mM NaF, 1 mM phenylmethylsulfonyl fluoride 1 mM sodium orthovanadate, 10 μg/mL aprotinin, 50 μg/mL leupeptin, and 1 μg/mL pepstatin A). The resected tumor samples are homogenized with lysis buffer containing 25 mM β-glycerophosphate and 0.5% (v/v) phosphatase inhibitor cocktail 2 at 4 °C. Cellular debris is removed by centrifugation at 17 860g for 20 min at 4 °C. Aliquots of the supernatants containing 5-20 μg of protein are subjected to SDS-PAGE under reducing conditions. The proteins are then transferred onto PVDF membranes, blocked with TBS containing 0.05% Tween-20 and either 5% skim milk or 5% BSA. The membranes are probed with the following antibodies: anti-c-Met polyclonal antibody (C-28) and anti-VEGFR-2 polyclonal antibody (C-20); mouse anti-phosphotyrosine clone 4G10; and anti-VEGFR-2 polyclonal antibody, anti-phospho-VEGFR-2 (Tyr996) polyclonal antibody, and anti-phospho-c-Met (Tyr1234/1235) polyclonal antibody. Detection is performed using a Super Signal enhanced chemiluminescence kit. Immunoreactive bands are visualized by chemiluminescence with an Image Master-VDS-CL detection system. The intensity of each band is measured by using an image analyzer.
細胞アッセイ 細胞株 MKN45, EBC-1, Hs746T, SNU-5, A549, SNU-1 and MKN74
濃度 5-5000 nM
反応時間 3 days
実験の流れ Cells (1–3 × 103 cells/100 μL/well) are seeded on 96-well culture plates with various concentrations of E7050 and cultured for 3 days. Then, 10 μL of WST-8 reagent is added to each well, and absorbance is measured at 450 nm compared with a reference measurement at 660 nm using a MTP-500 microplate reader. HUVEC (2 × 103 cells/well) are cultured for 3 days in medium containing HGF (30 ng/mL), VEGF (20 ng/mL), or basic fibroblast growth factor (bFGF) (20 ng/mL) together with serially diluted E7050.
動物実験 動物モデル Subcutaneous xenograft models
投薬量 50–200 mg/kg
投与方法 orally once a day

カスタマーフィードバック

Data from [Data independently produced by , , Mol Cancer Ther, 2017, 16(3):506-515]

Data from [Data independently produced by , , Mol Cancer Ther, 2017, 16(3):506-515]

Data from [Data independently produced by , , Cancer Sci, 2017, 108(7):1378-1385]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

E7050 Suppresses the Growth of Multidrug-Resistant Human Uterine Sarcoma by Inhibiting Angiogenesis via Targeting of VEGFR2-Mediated Signaling Pathways [ Int J Mol Sci, 2023, 24(11)9606] PubMed: 37298555
Blockade of c-Met-Mediated Signaling Pathways by E7050 Suppresses Growth and Promotes Apoptosis in Multidrug-Resistant Human Uterine Sarcoma Cells [ Int J Mol Sci, 2022, 23(23)14884] PubMed: 36499211
MET amplification results in heterogeneous responses to osimertinib in EGFR-mutant lung cancer treated with erlotinib [ Cancer Sci, 2020, 111(10):3813-3823] PubMed: 32735723
Diverse Receptor Tyrosine Kinase Phosphorylation in Urine-Derived Tubular Epithelial Cells from Autosomal Dominant Polycystic Kidney Disease Patients [ Nephron, 2020, 1-12] PubMed: 32799196
LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis [ Cell, 2019, 178(6):1478-1492] PubMed: 31474362
MET Copy Number Gain Is Associated with Gefitinib Resistance in Leptomeningeal Carcinomatosis of EGFR-mutant Lung Cancer [Nanjo S Mol Cancer Ther, 2017, 16(3):506-515] PubMed: 28138027
Impact of MET inhibition on small-cell lung cancer cells showing aberrant activation of the hepatocyte growth factor/MET pathway. [Taniguchi H, et al. Cancer Sci, 2017, 108(7):1378-1385] PubMed: 28474864
In vivo imaging xenograft models for the evaluation of anti-brain tumor efficacy of targeted drugs [Kita K Cancer Med, 2017, 6(12):2972-2983] PubMed: 29125233

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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